Quaglia W, Brasili L, Cristalli G, Giardinà D, Picchio M T, Melchiorre C
Department of Chemical Sciences, University of Camerino, Italy.
J Med Chem. 1988 Sep;31(9):1861-6. doi: 10.1021/jm00117a030.
Several N'-substituted N,N''-(dithiodi-2,1-ethanediyl)bis(1, omega-alkanediamines) were prepared and evaluated for their blocking activity on alpha-adrenoreceptors in the isolated rat vas deferens and human blood platelets. The results were compared with those obtained for benextramine (N,N''-(dithiodi-2,1-ethanediyl)bis[N'-[(2-methoxyphenyl)-methyl]- 1 ,6- hexanediamine], 10). Bendotramine (N,N''-(dithiodi-2,1-ethanediyl)bis[N'-[(2-methoxyphenyl)- methyl]-1,12-dodecanediamine], 16) proved to be as active as 10 on alpha 1-adrenoreceptors, showing that optimum activity is associated with two carbon chain lengths separating inner from outer nitrogens of tetraamine disulfides. On the other hand, 16 had no activity up to 20 microM at alpha 2-adrenoreceptors. The optimum activity at this receptor subtype was associated with a six to eight carbon chain (10-12). Furthermore, 10 proved to be more selective toward alpha 2-adrenoreceptors whereas 16 was a selective alpha 1-antagonist. The tetraamine disulfides were shown also to be potent inhibitors of human platelet aggregation induced by ADP or epinephrine. The potency increased with the carbon chain length. However, the results on platelets did not parallel those found in the rat vas deferens, indicating that differences exist between the alpha-adrenoreceptor subtypes investigated. In conclusion, 10 may be a useful tool in characterizing alpha 2-adrenoreceptors whereas 16 might help in investigating alpha 1-adrenoreceptors.
制备了几种N'-取代的N,N''-(二硫代二-2,1-亚乙基)双(1,ω-链烷二胺)，并评估了它们对离体大鼠输精管和人血小板中α-肾上腺素能受体的阻断活性。将结果与苯苄胺（N,N''-(二硫代二-2,1-亚乙基)双[N'-[(2-甲氧基苯基)-甲基]-1,6-己二胺]，10）的结果进行了比较。苄曲明（N,N''-(二硫代二-2,1-亚乙基)双[N'-[(2-甲氧基苯基)-甲基]-1,12-十二烷二胺]，16）在α1-肾上腺素能受体上的活性被证明与10相同，表明最佳活性与四胺二硫化物的内外氮之间相隔的两个碳链长度有关。另一方面，16在α2-肾上腺素能受体上高达20微摩尔时没有活性。该受体亚型的最佳活性与六至八个碳链（10 - 12）有关。此外，10被证明对α2-肾上腺素能受体更具选择性，而16是一种选择性α1-拮抗剂。四胺二硫化物也被证明是ADP或肾上腺素诱导的人血小板聚集的有效抑制剂。效力随碳链长度增加。然而，在血小板上的结果与在大鼠输精管中发现的结果不一致，表明所研究的α-肾上腺素能受体亚型之间存在差异。总之，10可能是表征α2-肾上腺素能受体的有用工具，而16可能有助于研究α1-肾上腺素能受体。
